Analysis of Registered Clinical Trials in Gastroenterology, 2007-2019
Authors: Nirosha D. Perera, Marija Kamceva, Jolie Z. Shen, Brandon E. Turner, Maya Abdou, Jecca R. Steinberg, Amit Mahipal
Journal: JAMA Network Open (2022)

IntroductionEvidence-based medical decisions rely on comprehensive clinical trial data.A previous study 1 found that gastrointestinal (GI) clinical trials were often limited, seldom using rigorous methods.This study investigated features of GI trials registered on ClinicalTrials.gov,analyzing factors associated with early discontinuation, results reporting, and methodological rigor. MethodsStanford University determined that this cross-sectional study was exempt from institutional review board approval and informed consent because all clinical trial data were publicly available.This report follows the STROBE reporting guideline for observational studies.Using a previously published protocol, 1-3 we applied medical subject heading (MeSH) terms (eMethods in the Supplement) to identify 22 339 potential GI trials registered on ClinicalTrials.govbetween October 1, 2007, and December 31, 2019.The Clinical Trials Research Team manually reviewed and categorized trial disease focus and anatomic location (eMethods in the Supplement).Characteristics extracted from ClinicalTrials.govincluded funding source (industry, US government, or academic sources) and enrollment number.Rigorous methodology was defined as being randomized, double blinded, multisite, and overseen by a data and safety monitoring committee (DMC) and having 50 or more patients enrolled.Primary outcomes were early discontinuation and results reporting.Missing data were addressed via multiple imputations using a published protocol. 2,3 ResultsA total of 20 548 trials contained true GI content, representing 7 million participants (7 167 700 individuals).Most trial funding sources were academic (58.3%), followed by industry (35.6%) and US government (6.1%)sources.Total trial number increased by 32.6% from the 2007 to 2013 period to the 2014 to 2019 period, while the proportion of clinical trials that were GI trials remained static, beginning at 9.2% in 2008 and ending at 8.8% in 2019, with a peak in 2011 of 10.2% (Figure).The mean annual growth rate of academic-funded trials was 10.9%, compared with 0.60% and -0.40% for government-and industry-funded trials, respectively.Most trials focused on neoplasia (42.6%; mostly US government funded) or infection (16.0%; mostly industry funded), and most trials focused on the liver or colorectal regions (30.1% and 24.1%, respectively).US government-funded trials had the lowest adjusted hazard ratio (aHR) for early discontinuation vs other funding sources (Table) and the highest rate of results reporting (25.3% vs 5.4% for academic funding; P < .001).Estimated enrollment had the highest aHRs in associations with early discontinuation (Table ).Most trials had no DMC oversight (58.6%) and took place at a single site (59.4%) and in North America (36.7%) or Europe (29.1%).Among phase 3 trials, 12.0% used our definition of rigorous methodology.US government-funded trials had the highest proportion of trials meeting this definition (19.0%), while academic-funded trials had the lowest proportion (5.3%).